Chronic kidney disease (CKD), also known as chronic renal disease, is a progressive loss in renal function over a period of months, or years. The most severe stage of CKD is End Stage Renal Disease (ESRD), which occurs when the glomerular filtration rate (GFR) is lower than 15 mL/min. In the U.S., the two main causes of CKD are diabetes and high blood pressure, which are responsible for up to two-thirds of the cases. Heart disease is the leading cause of death for all people having CKD. Excessive fluid can accumulate in patients suffering from ESRD. The mortality rate of ESRD patients who receive traditional hemodialysis therapy is 24% per year with an even higher mortality rate among diabetic patients. Fluid accumulates in ESRD patients because the kidneys can no longer effectively remove water and other compounds from the body. The fluid accumulates first in the blood and then accumulates throughout the body resulting in swelling of the extremities and other tissues as edema. This accumulation of fluid causes increased stress on the heart causing significant increases in blood pressure or hypertension, which can lead to heart failure. Hypertension is the single most important predictor of coronary artery and cerebrovascular diseases and is the most predominant comorbidity among patients with ESRD, with a prevalence of approximately 80%. Accordingly, an objective of ESRD treatment is to render patients euvolemic and normotensive effectively. Medicare recognizes the severity of this problem by mandating that each ESRD patient's treatment plan “render the patient euvolemic and normotensive”—specifically, blood pressure (BP) should be “reduced to ≦130/80 with minimal use of medications.” Chronic fluid overload and inability to maintain dry weight plays a major role in the generation and prevalence of hypertension among ESRD patients. The ability to provide daily ultrafiltration (UF), and maintain dry weight would contribute to the control of hypertension by decreasing the need for UF during hemodialysis sessions, and could theoretically decrease, the number of hemodialysis (HD) treatments per week. The reduction in hemodialysis treatment time would address some of the pressing medical and economic issues surrounding the treatment of ESRD patients.
Although the population of patients afflicted with CKD grows each year, there is no cure. Current treatments for CKD seek to manage comorbidities and, if possible, slow the progression of the disease. However, as the disease progresses, renal function decreases and eventually renal replacement therapy is employed to compensate for lost kidney function. Renal replacement therapy entails transplantation of a new kidney, or, dialysis. The excess fluid accumulated in patients suffering from CKD is generally removed by direct ultrafiltration or by the ultrafiltration action of a dialysis procedure. These procedures are carried out three times a week in three to five hour, sessions. Dialysis emulates kidney function by removing waste solutes and excess fluid from a patient's blood. During dialysis, the patient's blood that contains high concentration of waste solutes is exposed to a semi-permeable membrane in contact with a solute-deficient dialysate. Solute removal is accomplished via diffusion across the membrane, while fluid removal is accomplished via pressure-driven ultrafiltration. Once the blood is purified, it is then returned to the patient. Although effective at removing wastes from blood, dialyses treatments are administered intermittently and therefore do not emulate the continuous function of a natural kidney. Moreover, there are many inconveniences associated with dialysis, such as the necessity of committing to time consuming, thrice weekly treatments. Many patients eventually elect to forgo treatment on this basis alone. Additionally, several complications are associated with dialysis, resulting from the sporadic nature of conventional treatment regimens. These complications include blood pressure and electrolyte concentration fluctuation, vascular abnormalities, anemia, nausea, and fatigue. In severe cases, removal of the large amounts of fluid may even lead to arrhythmias and heart failure. Once the dialysis session is completed, the fluid begins to accumulate again in the tissues of the patient.
The benefits of dialysis notwithstanding, statistics indicate that three out of five dialysis patients die within five years of commencing treatment. Increasing the frequency and duration of dialysis sessions more closely resembles the continuous kidney function sought to be emulated. In addition, there are several advantages to treating patients suffering from fluid overload with ultrafiltration rather than diuretic drugs. Ultrafiltration offers an efficient fluid removal process without the side effects observed with use of pharmaceuticals, such as kidney failure and drops in blood pressure. Ultrafiltration and/or hemofiltration expose blood to a semi-permeable membrane under transmembrane pressure. The membrane's properties provide that water, salts, and other particles of small molecular weight pass through the membrane, while blood cells, proteins, and other molecules of larger molecular weight do not. An ultrafiltration cartridge is generally made up of a large number of small diameter hollow fiber type membranes. Typically, blood is accessed from the patient via a pair of needles placed in a fistula or a graft, or a catheter placed in an artery or large vein and is pumped into the ultrafiltration cartridge to generate the pressure to carry out the ultrafiltration process. The blood goes through the inner lumens of the hollow fibers, and the filtrate goes to the inter-fiber space and is removed. The treated blood is then returned to the patient.
These conventional ultrafiltration procedures have several disadvantages. As with dialysis, which may be performed at the same time for renal disease patients, a patient's mobility is limited because the processes are carried out extracorporeally using large, fixed machines. The most common complications in performing extracorporeal fluid removal are cardiovascular instability, hypotension, and shock. These events seem to be correlated with ultrafiltration rate. When the rate of ultrafiltration exceeds 0.25 mL/min/kg, the chance of hypotensive episodes increases exponentially. The cause of these complications is the discrepancy between the speed of fluid extraction by the ultrafiltration device and the rate of intravascular refilling from the interstitial and intracellular space within the patient. Long-term blood access necessary for the operation of ultrafiltration and hemodialysis devices can also be problematic. Vascular access devices such as percutaneous catheters used in hemodialysis patients may cause complications such as bleeding, infection, and clotting. Interactions between blood components and the materials found within blood processing systems could induce the activation of several biological systems such as platelets, complement, and coagulation cascades. Accordingly, conventional blood processing systems typically employ the use of anticoagulant drugs, such as heparin, to prevent the formation of blood clots. Prolonged use of anticoagulant drugs presents a significant risk of uncontrolled bleeding in patients.
In continuous hemofiltration or hemodialysis, blood is filtered and dialyzed without interruption. These procedures enable the removal of large volumes of fluid while avoiding the hypotensive episodes caused by intermittent hemodialysis, and are indicated for managing patients with acute renal failure who are hemodynamically unstable, require large volumes of fluid, or both. In continuous hemofiltration, water and solutes up to a certain molecular weight filter from the blood by convection through a permeable membrane, the filtrate is discarded, and the patient must receive infusions of physiologically balanced water and electrolytes. A dialysis circuit can be added to the filter to improve solute clearance. These procedures may be arteriovenous or venovenous. Arteriovenous procedures thus have the benefit of being a simple system in which arterial pressure is sufficient to push blood through the filter into the femoral vein without using a pump. However, filtration rates are typically low for continuous arteriovenous procedures, especially in hypotensive patients. In continuous venovenous procedures, a pump is employed to push blood from one large vein through the dialysis circuit and back into the venous circulation. Using a double-lumen catheter, blood is drawn from and returned to the same vein.
Some examples of prior art devices for dialyzing blood teaching use of various membranes, inlets and outlets are listed below.
U.S. Pat. No. 3,370,710 teaches a blood dialyzing apparatus with a pleated membrane and having a first fluid inlet and outlet pair, and a second fluid inlet and outlet pair.
U.S. Pat. No. 3,809,241 teaches a portable kidney, coil of a portable dialysate delivery system utilizing a self-contained re-circulating source of dialysate solution or a single-pass dialysate proportioning system. The output of the artificial kidney within the dialysate pumping and delivery system is via a tube and an output tube in which dialysate exits. The output of a blood pump enters the artificial kidney via a tube, and the outlet of the blood circuit system from the artificial kidney is at another tube.
US 2008/0006570 teaches a chambered cartridge for treating medical or biological fluids. The cartridge, which may be rigid or flexible, includes at least one inlet and one outlet and a plurality of separators.
US 2006/0076295 teaches a wrist-wearable dialysis system having a dialyzer and a pump having first, second and third inlet channels, first, second and third exit channels and a microfluidic extraction channel connected to the first, second and third inlet channels and the first, second and third exit channels and a flush port.
US 2010/0022936 teaches a component of a wearable ultrafiltration device having a blood inlet tube leading from a first blood vessel, a blood pump, an anticoagulant reservoir for infusing anticoagulants into the blood, a blood filter including a substrate through which the blood is circulated and filtered, a fluid bag for storing the excess fluid and a blood outlet tube leading to a second blood vessel. Hollow fibers are also taught wherein excess fluid is drained from the hollow fibers, which act as a sieve such that excess fluid passes through, but not blood.
Portable devices for hemodialysis or ultrafiltration in the form of wearable devices are generally large and cumbersome. Hence, there is a need for an implantable device that can provide both hemodialysis and/or ultrafiltration to a patient in a configuration of blood and dialysate flow across a membrane that is suitable for small volumes in a portable or implantable dialyzer. The need extends to providing methods for cleaning wherein the device can be used without decrement for a prolonged period, ideally for the expected life of the device, without the need for heparin, citrate or other anti-coagulants. Such a device would lower the very substantial costs to the healthcare system in treating patients with acute or chronic renal failure or CHF by enabling new modalities of outpatient, home or ambulatory treatment. Patients would benefit from fewer anticoagulant-related complications, less medication, less hospitalization and improved quality of life.
There is also a need for a device that provides continuous hemofiltration or continuous hemodiafiltration that would enhance patient mobility and reduce complications related to vascular access and extracorporeal blood processing. Furthermore, there is a need for an implantable hemodiafiltration device capable of operating at a pressure similar to that of a patient's blood pressure, and at a rate similar to that of natural kidney function to provide more consistent and beneficial therapy as compared to existing intermittent treatment regimens. Additionally, an implantable device used for dialysis or ultrafiltration is needed that would eliminate the need for visiting a dialysis clinic for treatments, and improve patient compliance with dialysis prescriptions. An implantable hemodiafiltration device used for dialysis or ultrafiltration operable at a patient's average blood pressure would thus permit blood, treatment schedules that are suitable and adaptable to a patient's lifestyle, thereby promoting patient health and enhancing patient quality of life.